Fig. 3: Combination of sorafenib and LZX-2-73 led to an increase in ROS accumulation.

ROS or mitochondrial ROS production was detected using CellROX (A) or MitoSOX (B), respectively, by flow cytometry analysis on MIAPaCa-2 cells incubated for 24 h with sorafenib, LZX-2-73, or their combination. Statistical significance is indicated as follows: *p < 0.05, **p < 0.01, ***p < 0.001 (1-way ANOVA, Dunnett’s test, compared to combinatory treatment). (n = 3). C OXPHOS metabolism, reflected by oxygen consumption rate (OCR) levels were measured on MIAPaCa-2 cells incubated for 24 h with sorafenib, LZX-2-73, or their combination Levels of lipid peroxidation, indicated by MDA levels (D) or by the oxidation of the BODIPY-C11 probe (E) (measured via fluorescence microscopy to monitor the oxidized and non-oxidized variants of lipid peroxides), were assessed in cells treated with sorafenib, LZX-2-73, or the combination of both drugs for 72 h. Statistical significance is indicated as follows: *p < 0.05, **p < 0.01, ****p < 0.0001 (1-way ANOVA, Dunnett’s test, compared to combinatory treatment) (n = 3). Scale bar: 50 μm.